The aim of this proposal is to identify and characterize novel long noncoding RNAs (lncRNAs) that function to control inflammation and viability in macrophages. Macrophages are critical effector cells of the innate immune system where they function to control infection and maintain tissue homeostasis. In Aim 1 we will perform an unbiased screen to knockdown all lncRNAs in human or murine macrophages using CRISPRi technology and determine those that function to control NF?B, the master regulator of inflammatory genes. In Aim 2 of this proposal we will identify all lncRNAs required for macrophage viability in humans and mice. We will determine the mechanism of actions of our top conserved candidates. This proposal will allow for rapid meaningful data on the role that lncRNAs play in macrophage biology to be obtained in a highly efficient manner.